{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:48:13Z","timestamp":1791107293240,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,3,15]]},"abstract":"<jats:p>Four naturally occurring flavones (baicalein, quercetin, quercetagetin and myricetin) and two novel catechins [(-)-epicatechin gallate and (-)-epigallocatechin gallate, from the tea plant Camellia sinensis], which are known inhibitors of reverse transcriptase, were shown to induce mammalian topoisomerase II-dependent DNA-cleavage in vitro. The flavones differed from the catechins in causing unwinding of duplex DNA, but both classes of compound induced enzymic DNA breakage at the same sites on DNA. Moreover, the cleavage specificity was the same as that for the known intercalator 4\u2032-(acridin-9-ylamino)methanesulphon-m-anisidide, suggesting that these agents trap the same cleavable complex. Analysis of some 30 flavonoid compounds allowed elucidation of the structure-function relationships for topoisomerase II-mediated DNA cleavage. For flavonoid inhibitors an unsaturated double bond between positions 2 and 3 of the pyrone ring and hydroxy groups at the 5, 7, 3\u2032 and 4\u2032 positions favoured efficient cleavage. Hydroxy substitutions could be tolerated at the 3, 6 and 5\u2032 positions. Indeed, the absence of substituents at the 3\u2032, 4\u2032 and 5\u2032 positions could be compensated by a hydroxy group at position 6 (baicalein). Similar requirements have been reported for flavonoid inhibitors of protein kinase C that act competitively with ATP, suggesting interaction with a conserved protein feature. Formation of the cleavable complex is a cytotoxic lesion that may contribute to the growth-inhibitory properties of flavones observed for three human tumour cell lines. These results are discussed in regard to the selectivity of antiviral agents.<\/jats:p>","DOI":"10.1042\/bj2820883","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:25:44Z","timestamp":1439241944000},"page":"883-889","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives"],"prefix":"10.1042","volume":"282","author":[{"given":"C A","family":"Austin","sequence":"first","affiliation":[{"name":"Molecular Genetics Group, Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Patel","sequence":"additional","affiliation":[{"name":"Molecular Genetics Group, Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Ono","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Oncology, Aichi Cancer Centre Research Institute, Nagoya 464, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Nakane","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Oncology, Aichi Cancer Centre Research Institute, Nagoya 464, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Fisher","sequence":"additional","affiliation":[{"name":"Molecular Genetics Group, Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/282\/3\/883\/606264\/bj2820883.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/282\/3\/883\/606264\/bj2820883.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T21:50:17Z","timestamp":1637704217000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/282\/3\/883\/27833\/Site-specific-DNA-cleavage-by-mammalian-DNA"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,3,15]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1992,3,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj2820883","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,3,15]]}}}